Nucleosides, Nucleotides & Nucleic Acids最新文献

This paper remembers Lynette Fairbanks, a Principal Clinical Biochemist, working at the Purine Research Laboratory of Guy's and St Thomas' Hospitals, London, England, founded by Anne Simmonds. She was a driving force in the laboratory guiding research and screening for inborn errors of metabolism, while she was a great supervisor. Just being retired she passed away in January 2023.

This work is focused on the synthesis of several transition metal complexes [ML(MA)], where M = Copper (II), Zinc (II), Cobalt (II) and Nickel (II), MA = maleic acid and L = Schiff base generated from benzene-1,2-diamine [o-phenylenediamine] and 4-chlorobenzaldehyde. The characterization using Fourier-Transform Infrared, Nuclear Magnetic Resonance spectroscopy, Ultraviolet-Visible spectra, Mass, Electro Paramagnetic Resonance and elemental analysis confirm the square planar geometry of the complexes. The in vitro antimicrobial potential of the complexes has been tested by the broth dilution method and the antioxidant method has been done by free radical scavenging analysis. The in vitro methods reveal the outstanding biological characteristics of the copper complexes. The molecular structure of the ligand and its metal (II) complexes has been optimized using Density Functional Theory studies performed by the Gaussian-09 software and their parameters have been discussed. Natural Bond Orbital and Frontier Molecular Orbital analyses have assessed the presence of a metal-ligand bond in complexes. In addition, molecular docking studies have also been performed on antiviral activity of all the complexes using a viral protein and their interacting amino acids.

Background and objective: Cyclin-dependent protein kinases (CDKs) have been suggested as prospective therapeutic targets because they control processes vital to the survival and growth of cancer cells. However, research on the varied CDK expression profiles and prognostic factors in osteosarcoma is still lacking.

Methods: The osteosarcoma microRNA (GSE65071) and gene expression profiles were retrieved from the Gene Expression Omnibus (GEO) database (GSE42352). A substantial variation in prognosis was discovered in CDKs using the TARGET database. Cytoscape was used to construct the miRNAs-CDKs network, and functional and pathway enrichment analyses were completed. It was looked at how immune checkpoint genes, m6A-related genes, and CDKs interact.

Results: In patients with osteosarcoma compared to normal samples, CDK1-5, CDK18, CDK16, and CDK17 gene expression levels were considerably greater, whereas CDK7-9, CDK11B, CDK16, and CDK20 gene expression levels were significantly lower. Patients with osteosarcoma who had low CDK3 and 18 gene levels or high CDK6, 9 gene levels were predicted to have a favorable prognosis and a long-life expectancy. Immune checkpoint genes, m6A-related gene expression, and CDKs expression all showed some connection. Finally, a network of crucial CDKs and miRNAs was constructed.

Conclusion: According to our research, CDK3, 6, 9, and 18 have been identified as possible therapeutic targets for osteosarcoma, and CDKs may have a role in controlling m6A mutations in tumor cells as well as immune checkpoint regulation.

Advancements in DNA nanotechnology have led to new exciting ways to detect cell-free tumor biomarkers, revolutionizing cancer diagnostics. This article comprehensively reviews recent developments in this field, discussing the significance of liquid biopsies and DNA nanomachines in early cancer detection. The accuracy of cancer diagnosis at its early stages is expected to be significantly improved by identifying biomarkers. Liquid biopsies, offering minimally-invasive testing, hold the potential for capturing tumor-specific components like circulating tumor cells, cell-free DNA, and exosomes. DNA nanomachines are advanced molecular devices that exploit the programmability of DNA sequences for the ultrasensitive and specific detection of these markers. DNA nanomachines, nanostructures made of DNA that can be designable and switchable nanostructures, have a wide range of advantages for detecting tumor biomarkers, including non-invasiveness, affordability, high sensitivity, and specificity. Scientists also work on dealing with challenges like low marker concentrations and interference, which are addressed through microfluidic integration, nanomaterial amplification, and indirect signal detection. Despite advances, multiplex detection remains a challenge. In conclusion, DNA nanomachines bear immense promise for cancer diagnostics, advocating personalized treatment and improving patient outcomes. Continued research could redefine how we find and treat tumors, leading to better patient outcomes.

Objective: The objective of the study was to assess the potential association between the indel polymorphism (rs34802628) located within the intron of the collagen type ⅳ alpha 2 gene (COL4A2) and the susceptibility to stomach adenocarcinoma (STAD) within a Chinese population.

Methods: Peripheral venous blood samples were collected from a total of 497 STAD patients and 804 healthy control individuals to extract genomic DNA. The genotyping of the COL4A2 rs34802628 polymorphism was carried out using a polymerase chain reaction assay. Additionally, statistical analyses were conducted on the expression levels of COL4A2 mRNA using the GEPIA database. Meanwhile, the expression of COL4A2 mRNA was also validated by Real-time PCR using STAD tissue samples. Then, based on an analysis of patient tumor RNA seq data available from the Cancer Genome Atlas (TCGA), we assessed the prognostic value of mRNA expression of the COL4A2 gene in STAD patients using K-M plotter.

Results: The study presented compelling evidence supporting an association between the rs34802628 polymorphism in the COL4A2 gene and susceptibility to STAD. Logistic regression analysis revealed that both the heterozygote and homozygote 4-bp del/del genotypes were significantly associated with a decreased risk of STAD, even after controlling for other variables (adjusted odds ratio [OR] = 0.663, 95% confidence interval [CI] 0.519-0.848, p = 0.037; OR = 0.422, 95% CI 0.290-0.614, p = 0.000005, respectively). Importantly, individuals carrying the 4-bp deletion allele demonstrated a notably lower risk of developing the disease (OR = 0.696, 95% CI 0.591-0.820, p = 0.000014). Furthermore, Genotype-phenotype correlation studies in human STAD tissue samples demonstrated that the higher mRNA expression levels of COL4A2 were associated with the ins allele of rs34802628. Bioinformatics analysis revealed that higher expression of the COL4A2 gene was significant with development and poor prognosis of STAD.

Conclusion: The results of our study provide strong evidence indicating a potential involvement of genetic variants in the COL4A2 gene in the development of STAD. Nonetheless, to validate and consolidate these findings, additional investigations incorporating larger sample sizes and functional experiments are necessary.

The inflammatory cytokine resistin, which is encoded by the RETN gene, plays a variety of roles in cancer. This study aimed to assess the relationship between RETN gene expression and cancer stage, survival prognosis, immune infiltration, and drug sensitivity, and whether the rs3219175 G > A polymorphism affected the expression of the RETN gene and cancer risk. The clinical significance of RETN gene expression and the rs3219175 polymorphism in cancer was analyzed by the GSCA platform, GTEx database and STATA software. The results showed that RETN gene expression was associated with the stage of thyroid carcinoma, survival prognosis and immune infiltration of certain cancers, and sensitivity to multiple drugs. The rs3219175 polymorphism could influence the expression of the RETN gene in a wide range of tissues. Furthermore, RETN gene rs3219175 polymorphism was significantly associated with cancer risk [GA vs. GG: OR = 2.27, 95%CI = 1.26-4.09; (GA + AA) vs. GG: OR = 2.23, 95%CI = 1.28-3.88; A vs. G: OR = 1.72, 95%CI = 1.15-2.58]. In conclusion, the current study suggested that resistin might serve as a prognostic marker and therapeutic target for certain cancers, and the rs3219175 polymorphism might be used as a marker for predicting cancer risk.

This study aimed to investigate the impact of Free-fatty acid receptor-4 (FFAR4) rs61866610 polymorphism on colorectal cancer (CRC) risk. Herein, ninety-two histopathologically confirmed CRC patients and 95 healthy individuals were evaluated for FFAR4 polymorphism by RFLP-PCR. Gender, age, body mass index (BMI), underlying disease, and smoking status were recorded for all subjects. Clinical and histopathologic findings including tumor grade and TNM stage were also prepared in the patient group. Except for type 2 diabetes which was more prevalent in the control group, there were no differences between the two groups regarding underlying diseases (p > 0.05). The frequency of genotypes was as follows: in the CRC group 75% wild type, 23.9% heterozygous, and 1.1% homozygous mutant. In the control group 85.3% wild type, 12.6% heterozygous, and 2.1% homozygous mutant. Mutant allele carriers were more frequent in CRC subjects (25%) than in the normal group (14.7%) but it did not reach a significant level. The frequency of mutant genotypes in colon cancer and rectal cancer was 27.5% and 8.3% respectively (p = 0.282). The mutant genotypes were found more in patients with high-grade tumors (p = 0.154). Subjects with stage III/IV had a higher frequency of mutant genotypes than low-stage cases (p = 0.011). No association was found regarding rs61866610 and obesity or type 2 diabetes (p > 0.05). In conclusion, FFAR4 (rs61866610) has no significant association with the risk of CRC, but the higher frequency of mutant genotypes in subjects with advanced cancer stages (III/IV) suggests further studies to determine the role of FFAR4 in colorectal tumorigenesis.

Efficient and safe extraction of microRNAs (miRNAs) from biological samples is pivotal for genetic regulation studies and biotechnological applications. This study focuses on optimizing the microRNA extraction process from the plasma of common carp, a significant species in aquaculture. Recognizing the limitations and hazards of commercial extraction kits, which often employ toxic chemicals like phenol and chloroform, we sought to develop a safer and more effective alternative. Our optimized protocol utilizes guanidinium isothiocyanate (GITC) and sarkosyl, omitting hazardous substances. We explored several parameters including GITC concentration, the addition of sarkosyl, and the role of sodium chloride in enhancing miRNA yield. Our findings demonstrate that optimal conditions involve a GITC concentration of 4.2 M, a 3% sarkosyl concentration, and the use of sodium chloride at 0.5 M. We also investigated the utility of glycogen as a nucleic acid carrier, finding 160 µg to be the optimal concentration. Comparative analysis with commercial kits indicated our method provides higher miRNA yields with reduced cycle threshold values, underscoring the effectiveness of our custom protocol. This optimized approach not only enhances miRNA recovery but also emphasizes safety and cost-effectiveness, making it a valuable method for both research and practical applications in aquaculture.

The coronavirus disease 2019 (COVID-19) is a recent pandemic occurring worldwide due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, spreading mainly through large respiratory droplets or maybe through other transmission routes. The human genome has the most varied immune response genes correlated with infectious diseases. Genetic variants of mannose-binding lectin 2 (MBL2), an immunomodulatory gene, were associated with the risk, severity, and frequency of viral infections. In the present study, we hypothesized that the MBL2 gene rs1800450 variant could be associated with the development of COVID-19 disease in a Turkish population. Ninety-eight COVID-19 patients and 98 healthy, ethnically matched controls were studied. We isolated genomic DNA from whole blood and analyzed the MBL2 rs1800450 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Associations were analyzed with the SPSS 20 statistical software. We found that MBL2 rs1800450 genotype distribution was significantly different between patients and controls. The patients had a higher MBL2 rs1800450 AA genotype than the controls had (4.94% in patients vs. 3.12% in controls, p = 0.006). The subjects carrying AA genotype had a 10.83-fold increased risk for COVID-19 disease (OR = 10.83, %95 CI = 1.359-86.349). We could not detect any significant difference between the COVID-19 patients and healthy controls in allele frequencies. Our findings demonstrated that the MBL2 rs1800450 BB genotype might increase the susceptibility to COVID-19 disease in the Turkish population. We suggest further studies with a larger sample size and other ethnic populations.